DESCRIPTION: (verbatim) Tissue Engineering is defined as the science developing techniques for fabrication of new tissues for replacement and regeneration of lost tissues based on principles of cell and developmental biology. One of the major problems in aging, periodontal disease, tooth implants, transplantation, or replantation remains the repair of the periodontium and the regeneration of periodontal tissues such as cementum, periodontal ligament and alveolar bone. In general, to achieve complete repair and regeneration, it is necessary to recapitulate the process of embryogenesis and morphogenesis involved in the formation of that tissue. In the case of the periodontium, complete periodontal repair entails de novo cementogenesis, osteogenesis, and periodontal ligament fibers. Current strategies for periodontal repair have been directed at enhancing alveolar bone and periodontal ligament regeneration and have the problem that do not completely restore the architecture of the periodontium. The long-term objective of this project is to achieve complete periodontium regeneration by focusing on the cementum layer using tissue engineering to induce de novo cementogenesis. We propose to test the hypothesis that HERS cells maintained in vitro can re-colonize cementum denuded roots and recreate the process of cementogenesis. Furthermore, the cementum-like mineralized extracellular matrix deposited by these cells in vitro (or some of its components) will induce complete periodontal regeneration. We propose to test this hypothesis by using an Immortomouse-derived HERS cell line established in our laboratory to re-colonize root dentine in vivo. In similar experiments, the extracellular matrix produced by these cells and some of its isolated components (mainly enamel proteins) will also be tested for their inductive and reparative capability. The results obtained in this study can then be applied, alone or in conjunction with known techniques for bone regeneration, for the treatment of periodontal disease and to improve the long-term success of implants. The data generated in this study will also provide information related to the regulation of root formation and possible ways to improve the diagnosis, treatment, and prognosis of tooth loss due to aging or periodontal diseases.